title: Hydroxychloroquine-induced pigmentation in patients with systemic lupus erythematosus: a case-control study.
abstract: OBJECTIVE
  Hydroxychloroquine-induced pigmentation is not a rare adverse effect. Our data support the hypothesis that hydroxychloroquine-induced pigmentation is secondary to ecchymosis or bruising.
  
  
  OBJECTIVE
  To describe the clinical features and outcome of hydroxychloroquine (HCQ)-induced pigmentation in patients with systemic lupus erythematosus (SLE).
  
  
  METHODS
  In a case-control study conducted at a French referral center for SLE and antiphospholipid syndrome, 24 patients with SLE, with a diagnosis of HCQ-induced pigmentation, were compared with 517 SLE controls treated with HCQ.
  
  
  METHODS
  The primary outcome was the clinical features of HCQ-induced pigmentation. Skin biopsies were performed on 5 patients, both in healthy skin and in the pigmented lesions. The statistical associations of HCQ-induced pigmentation with several variables were calculated using univariate and multivariate analyses.
  
  
  RESULTS
  Among the 24 patients, skin pigmentation appeared after a median HCQ treatment duration of 6.1 years (range, 3 months-22 years). Twenty-two patients (92%) reported that the appearance of pigmented lesions was preceded by the occurrence of ecchymotic areas, which gave way to a localized blue-gray or brown pigmentation that persisted. Twenty-three patients (96%) had at least 1 condition predisposing them to easy bruising. Results from skin biopsies performed on 5 patients showed that the median concentration of iron was significantly higher in biopsy specimens of pigmented lesions compared with normal skin (4115 vs 413 nmol/g; P < .001). Using multivariate logistic regression, we found that HCQ-induced pigmentation was independently associated with previous treatment with oral anticoagulants and/or antiplatelet agents and with higher blood HCQ concentration.
  
  
  CONCLUSIONS
  Hydroxychloroquine-induced pigmentation is not a rare adverse effect of HCQ. Our data support the hypothesis that HCQ-induced pigmentation is secondary to ecchymosis or bruising.
authors.affiliation: Service de Médecine Interne, Centre de Référence National pour le Lupus Systémique et le Syndrome des Antiphospholipides, Université Paris 6, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Moez
authors.initials: M
authors.lastname: Jallouli
authors.forename: Camille
authors.initials: C
authors.lastname: Francès
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Piette
authors.forename: Du Le Thi
authors.initials: du LT
authors.lastname: Huong
authors.forename: Philippe
authors.initials: P
authors.lastname: Moguelet
authors.forename: Cecile
authors.initials: C
authors.lastname: Factor
authors.forename: Noël
authors.initials: N
authors.lastname: Zahr
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyara
authors.forename: David
authors.initials: D
authors.lastname: Saadoun
authors.forename: Alexis
authors.initials: A
authors.lastname: Mathian
authors.forename: Julien
authors.initials: J
authors.lastname: Haroche
authors.forename: Christian
authors.initials: C
authors.lastname: De Gennes
authors.forename: Gaelle
authors.initials: G
authors.lastname: Leroux
authors.forename: Catherine
authors.initials: C
authors.lastname: Chapelon
authors.forename: Bertrand
authors.initials: B
authors.lastname: Wechsler
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
authors.forename: Nathalie
authors.initials: N
authors.lastname: Costedoat-Chalumeau
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D003288:Contusions / Q000150:complications; D004438:Ecchymosis / Q000150:complications*; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects* / Q000627:therapeutic use; D017495:Hyperpigmentation / Q000139:chemically induced*; D007501:Iron / Q000378:metabolism; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine; D007501:Iron